Differential mechanisms of action of the trace amines octopamine, synephrine and tyramine on the porcine coronary and mesenteric artery

Abstract

Trace amines such as p- tyramine, p- octopamine and p- synephrine are found in low concentrations in animals and plants. Consumption of pre-workout supplements containing these plant-derived amines has been associated with cardiovascular side effects. The aim of this study was to determine the mechanisms of action of these trace amines on porcine isolated coronary and mesenteric arteries. Noradrenaline caused contraction of mesenteric arteries and relaxation of coronary arteries. In both tissues, all three trace amines induced contractions with similar potencies and responses were unaffected by the β-adrenoceptor antagonist propranolol (1 µM), the nitric oxide synthase inhibitor L-NNA (100 µM), or the TAAR-1 antagonist, EPPTB (100 nM). However, the contractile responses of mesenteric arteries, but not coronary arteries, were significantly reduced by depletion of endogenous noradrenaline. Mesenteric responses to all three amines were abolished in the presence of prazosin (1 µM) whereas residual contractile responses remained in the coronary artery which were inhibited by a high concentration (100 µM) of EPPTB. The results suggest complex responses of the coronary artery to the trace amines, with activity at α 1 -adrenoceptors and potentially TAARs other than TAAR-1. In contrast the actions of the amines on the mesenteric artery appeared to involve indirect sympathomimetic actions and direct actions on α 1 -adrenoceptors.

The Anti-inflammatory Effects of Aerobic Training and Octopamine Consumption in the Heart Tissue of Rats Fed Deep-Fried Oil

“…A molecule related to octopamine (N-trans-feruloyloctopamine) shows anti-steatohepatitis properties in a model of non-alcoholic steatohepatitis (22). It has been reported that octopamine increases many hemocyte functions, such as phagocytosis, and these changes would tend to mitigate the decline in immunity due to the loss of molecular resources (23).…”

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology

“…In fact, an increase in systolic blood pressure, following a high ingestion of tyramine, is known as the “tyramine pressor response” [ 48 ]. Some results suggest that the indirect sympathomimetic effects played by trace amines are not their only mechanisms of action in the vascular system, since they can interact with other receptors [ 49 ]. Evidence has been shown that trace amines, particularly tyramine, β-phenylethylamine and octopamine, act directly on α1- adrenoreceptors, generating different responses based on the vessel evaluated.…”

“…Tyramine and β-phenylethylamine are also able to promote a contractive response in guinea pig and rat isolated gut preparations, quite the opposite to what occurs in the presence of sympathomimetic amines [ 50 ]. Research carried out using a high concentration of an antagonist of TAAR1, called EPPTB (RO-5212773), has shown a reduction in the vasocontractile response in the porcine coronary artery [ 49 ]. Additionally, tyramine and β-phenylethylamine exhibit a partial antagonism at β1 and β2 adrenoceptors, while octopamine has shown a partial β1 agonism and a partial orthosteric antagonist in β2 adrenoceptors [ 35 ].…”

“…In this line, changes in synephrine related pathways have been associated to migraine due to possible abnormalities in neurotransmitters and trace amines and/or abnormal interactions with their receptors [ 88 ]. This discovery also provides indirect evidence suggesting that synephrine could induce vascular responses via TAAR receptors [ 49 ].…”

Racemic synephrine found in Citrus aurantium‐listing pre‐workout supplements suggests a non‐plant‐based origin

“…1 Citrus aurantium L. (Bitter orange) belongs to the Rutaceae family and has been incorporated in supplements as an ergogenic aid or a purported natural weight-loss agent. 2 The primary alkaloid, (±)-p-synephrine, is an isomer of the α 1 -adrenergic receptor agonist, phenylephrine (Figure 1) and vascular smooth muscle contraction 3 and promotes thermogenesis by stimulating β 3 -adrenoceptors. 4 The World Anti-Doping Agency (WADA) has listed synephrine and all optical isomers of synephrine in the monitoring programme, whereas other related compounds such as methylsynephrine (oxilofrine) and octopamine are prohibited in-competition.…”